Klippel‐Feil syndrome 4 (KFS4; MIM# 616549) is an autosomal recessive disorder caused by biallelic pathogenic variants in MYO18B and comprises, in addition to Klippel‐Feil anomaly (KFA), nemaline myopathy, facial dysmorphism, and short stature. We aim to outline the natural history of KFS4 and provide an updated description of its clinical, radiological, laboratory, and molecular findings. We comprehensively analyzed the medical records of 6 Saudi and 1 American patients (including 5 previously unpublished cases) with a molecularly confirmed diagnosis of KFS4. All patients had myopathy of varying severity that followed a slowly progressive or non‐progressive course, affecting primarily the proximal musculature of the lower limb although hand involvement with distal arthrogryposis and abnormal interphalangeal creases was also observed. KFA and characteristic dysmorphic features, including ptosis and bulbous nose, were observed in all but two patients. The causal MYO18B variants were a founder NM_032608.5:c.6905C>A; p.(Ser2302*) variant in the Saudi patients (P1‐P6) and a novel MYO18B homozygous variant (c.6660_6670del;p.[Arg2220Serfs*74]) in the American Caucasian patient (P7). We report the phenotypic and genetic findings in seven patients with KFS4. We describe the natural history of this disease, confirm myopathy as a universal feature and describe its pattern and progression, and note interesting differences between the phenotypes observed in patients with KFA and those without.

中文翻译：

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MYO18B相关的常染色体隐性隐性Klippel-Feil综合征与肌病和面部畸形的进一步描述

Klippel-Feil综合征4（KFS4; MIM＃616549）是由MYO18B中的双等位基因致病变异引起的常染色体隐性遗传疾病除了Klippel-Feil异常（KFA），肾上腺肌病，面部畸形和身材矮小外，还包括其他内容。我们旨在概述KFS4的自然历史，并提供其临床，放射学，实验室和分子发现的更新描述。我们全面分析了6例沙特阿拉伯和1例美国患者（包括5例以前未发表的病例）的病历，这些患者经分子确诊为KFS4。所有患者均患有严重程度不同的肌病，并伴有缓慢进行性或非进行性病程，主要影响下肢的近端肌肉组织，尽管也观察到手累及远端关节变态和异常指间折痕。除两名患者外，其他所有患者均观察到KFA和特征性畸形特征，包括上睑下垂和球鼻。因果关系MYO18B变体是创始人NM_032608.5：c.6905C> A；沙特患者（P1-P6）中的p。（Ser2302 *）变异体和美国白种人患者（P7）中的新型MYO18B纯合变异体（c.6660_6670del; p。[Arg2220Serfs * 74]）。我们报告了7名KFS4患者的表型和遗传学发现。我们描述这种疾病的自然病史，确认肌病为普遍特征并描述其模式和进展，并注意在患有KFA的患者和未患有KFA的患者中观察到的表型之间的有趣差异。